Striatal formation of 6-hydroxydopamine in mice treated with pargyline, pyrogallol and methamphetamine

P. C. Liao, Y. M. Kuo, Y. C. Chang, C. Lin, C. F.G. Cherng, L. Yu

研究成果: Article同行評審

14 引文 斯高帕斯(Scopus)

摘要

Formation of 6-hydroxydopamine (6-OHDA) has been posited in the striatum following methamphetamine treatment and plays a critical role in methamphetamine-induced nigrostriatal dopaminergic toxicity. We used high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to determine the formation of 6-OHDA by the treatments of methamphetamine combined with pargyline, a monoamine oxidase inhibitor, and pyrogallol, a catechol-O-methyl-transferase inhibitor, in female C57BL/6J mouse striatum. A substantial amount of 6-OHDA (9.9 ± 0.7 pg/mg wet tissue) was detected in mice treated with pargyline (100 mg/kg) and pyrogallol (25 mg/kg) in combination. Greater striatal 6-OHDA levels were observed in mice treated with combined pargyline, pyrogallol and methamphetamine (50 mg/kg) as compared to mice treated with combined pargyline and pyrogallol. However, mice treated with pargyline and pyragollol in combination followed by one and two doses of methamphetamine exhibited comparable striatal 6-OHDA levels (23.2 ± 4.3, 27.3 ± 1.3 pg/mg wet tissue) in our protocol. We conclude that blockade of the primary metabolic pathways of dopamine by inhibiting both monoamine oxidase and catechol-O-methyl-transferase activities is sufficient to induce 6-OHDA formation in the striatum. Acute 6-OHDA accumulation in the striatum can be potentiated by methamphetamine, a potent dopamine releaser, administration following such metabolic inhibitions.

原文English
頁(從 - 到)487-494
頁數8
期刊Journal of Neural Transmission
110
發行號5
DOIs
出版狀態Published - 2003 5月 1

All Science Journal Classification (ASJC) codes

  • 神經內科
  • 神經病學(臨床)
  • 精神病學和心理健康
  • 生物精神病學

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